1. Field of the Invention
The invention disclosed herein relates to methods and compositions for inducing an MHC class-I restricted immune response, controlling the nature and magnitude of the response, particularly a multivalent response, and promoting effective immunologic intervention in pathogenic processes. Disclosed herein are methods and compositions for inducing an immune response against various combinations of tumor-associated antigens, which can promote effective immunologic intervention in pathogenic processes.
2. Description of the Related Art
The American Cancer Society has estimated that over one million people get cancer each year, and that approximately one out of every two American men and one out of every three American women will have some type of cancer at some point during their lifetime.
Normal body cells grow, divide, and die in an orderly fashion. In cell proliferative diseases such as cancer, cells, instead of dying, continue to grow out of control and divide. Although there are many kinds of cancer, they usually start because of out-of-control growth of abnormal cells.
Usual treatment options for cancer include surgery, radiation therapy, and chemotherapy. A fourth branch of treatment, which is referred to as immunotherapy, has more recently become established. Immunotherapies are designed to help the immune system recognize cancer cells, and/or to strengthen a response against cancer cells in order to destroy the cancer. Immunotherapies include active and passive immunotherapies. Active immuotherapies attempt to stimulate the body's own immune system to fight the disease. Passive immunotherapies generally do not rely on the patient's immune system to attack the disease; instead, they use immune system components (such as antibodies) created outside of the patient's body.
The immune system can be categorized into two discrete effector arms, innate and adaptive immunity. Innate immunity involves numerous cellular components and soluble factors that respond immediately, but generally to foreign stimuli. Adaptive immunity is customized to respond specifically to precise epitopes from foreign agents. The adaptive immune response is further divided into two effector arms known as the humoral and cellular immune systems. The humoral arm is centered on the production of antibodies by B-lymphocytes while the cellular arm involves the cytolytic activity of cytotoxic T lymphocytes.
Cytotoxic T lymphocytes (CTL) do not recognize epitopes on the targeted antigens themselves. Rather, CTL detect fragments of antigens that are displayed on the surface of cells. As a result antigens are visible to CTL only after they have been processed by the cell and displayed on the surface of the cell. The antigen processing and display system of cells has been well established. CTL recognize short peptide antigens, which are displayed on the surface in non-covalent association with class I major histocompatibility complex molecules (MHC). These class I peptides are in turn derived from the degradation of cytosolic proteins.
Despite various types of cancer treatments, a continuing need exists for additional and more effective treatment alternatives. One such alternative envisions methodologies of medical treatment that require or benefit from an ability to initiate, stimulate, and/or enhance an immune response by immunization. These methodologies include those depending upon the creation of an immune response against a desired antigenic polypeptide and those that depend upon the initiation or modulation of an innate immune response. Thus one approach in the treatment of cancer is the manipulation of the immune system by use of a therapeutic anticancer vaccine.
To generate a vaccine or other immunogenic composition, an antigen or epitope against which an immune response can be mounted is introduced into a subject. Although neoplastic cancer cells are derived from and therefore are substantially identical to normal cells on a genetic level, many neoplastic cells are known to present tumor-associated antigens (TuAAs). These antigens can be used by a subject's immune system to recognize and attack the neoplastic cells as foreign. Unfortunately, neoplastic cells generally appear to be ignored by the host's immune system.
A number of different strategies have been developed in the art in an attempt to generate vaccines with activity against neoplastic cells; however, an effective and marketable product has not emerged. The present invention therefore serves to overcome the deficiencies in the art and provides a plurality of immunogenic compositions, disclosed herein, for targeting cancer or tumor cells.